The interaction of substituted and rigidly linked diquinolines with DNA.
Viscometric measurements with circular and sonicated rodlike DNA fragments were used to explore whether ring substituents or conformationally restricted linkers promote bifunctional intercalation amongst a series of binuclear 4-aminoquinolines bridged via their 4-amino group. We find that ligands comprising unsubstituted quinolines and piperazine or pyrazole linkages bisintercalate. Quinoline-substituted alkyl-linked dimers intercalate in either a mixed monofunctional-bifunctional mode or bind with only one of their chromophores intercalated depending on the nature of the substituents. Equilibrium dialysis measurements show that the binding affinity for calf thymus DNA of the compounds studied ranges from (1.2-12) . 10(4) M-1 in buffer of ionic strength 0.1. Both co-operative and antico-operative binding isotherms were obtained and there is evidence for a second binding mode for the piperazine-linked diquinoline at saturating binding levels. For this compound the high-affinity association constant decreases with increasing ionic strength, 3.4 cations being released per bound ligand molecule. Partition dialysis measurements with DNAs of differing base composition indicate that the compounds studied are either AT selective or sequence neutral depending on ligand structure. For example, the pyrazole linker imparts a marked specificity for binding to AT-rich DNA, whereas the piperazine linker does not. Kinetic measurements using the surfactant-sequestration method reveal that DNA-diquinoline complexes dissociate very rapidly by complex mechanisms with rate constants greater than 100 s-1 in buffer of ionic strength 0.1.
McFadyen
W D
WD
Centre for Chemistry and Physics, School of Science of Mathematics Education, University of Melbourne, Parkville, Australia.
Sotirellis
N
N
Denny
W A
WA
Wakelin
L P
LP
D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D004270:DNA, Circular / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D011804:Quinolines / Q000378:metabolism*; D013379:Substrate Specificity
D004269:DNA, Bacterial; D004270:DNA, Circular; D008024:Ligands; D011804:Quinolines; D004247:DNA